Genentech, Inc.

Hoffmann-la Roche Inc.

Bristol-myers Squibb Compnay

F. Hoffmann-la Roche Ag

Osi Pharmaceuticals, Inc.

Lukas C Amler

Francis Lee

John D Haley

Graeme Griffin

Mark C Benyunes

Jayantha Ratnayake

Guy L Cavet

Peter Shaw

Robert L Yauch

Sreedhara Alavattam

Craig R Fairchild

Mark Lackner

Joachim Moecks

Graham Alexander Ross

David A Eberhard

Chin-Yu Lin

Andreas Strauss

Fei Huang

Xia Han

Karen A Reeves

Ajay Pandita

Carol O'Brien

Merrill Birkner

Ru-Amir Walker

Zephania W Kwong Glover

Emma I Clark

Lada Mitchell

Christina H De Toledo Pelizon

Graham A Ross

Methods and compositions are provided to determine if a cancer is resistant to treatment with anti-mitotic agents, including treatment with T-DM1. The methods relate to determining if the ABCC3 gene is amplified and/or overexpressed in the cancer.

Genetic variations associated with drug resistance

The present application describes the use of low HER3 as a selection criterion for treating patients with a HER inhibitor, such as pertuzumab. It also describes the use of high HER2:HER3 ratio as a selection criterion for treating cancer patients, such as ovarian cancer patients, with a HER inhibitor, such as pertuzumab. In addition, the application describes the use of high HER3 as a selection criterion for treating cancer patients with a chemotherapeutic agent, for instance gemcitabine.

Predicting response to a HER inhibitor

The present invention describes polynucleotides that have been discovered to correlate to the relative sensitivity or resistance of cells, e.g., breast cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Eph receptors. These polynucleotides have been shown to have utility in predicting the resistance and sensitivity of breast cell lines to the compounds. Such polynucleotides comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., breast cancer, in which signaling through one or more of the aforementioned Src tyrosine and protein tyrosine kinases is involved with the disease process.

Identification of polynucleotides for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells

Methods of using EPHA2 for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in breast cells

Growing community of inventors

Foster City, CA, United States of America

Lukas C Amler